1. Field of the Invention
This invention relates to a therapeutic system for administering clonidine via intact skin to the systemic circulation to effect alpha-adrenergic stimulation, such as for treating hypertension.
2. Description of the Prior Art
There are several patents/patent applications that relate to bandages or skin patches for administering drugs transdermally to the systemic circulation. In this regard U.S. Pat. Nos. 3,742,951, 3,797,494 and 4,031,894 are believed to be most relevant.
U.S. Pat. No. 3,742,951 describes a 3-layer system or bandage for administering vasodilators transdermally. The bandage comprises a backing layer, a drug release rate controlling reservoir layer that contains the vasodilator, and a contact adhesive layer by which the bandage is attached to the skin. U.S. Pat. No. 3,797,494 describes a similar bandage for administering systemic drugs transdermally comprising a backing layer, a drug reservoir layer, a microporous membrane that controls the drug release rate, and a contact adhesive layer. U.S. Pat. No. 4,031,894 describes a bandage that is structured similarly to the bandage of U.S. Pat. No. 3,797,494. Its bandage contains scopolamine in the contact adhesive layer as well as in the drug reservoir layer such that the scopolamine is administered in an initial priming dose followed by a continuous, substantially constant dosage for up to seven days.
The skin patch of the present invention is designed specifically to administer clonidine transdermally. In this regard the hypotensive properties of clonidine base, derivatives thereof, and related compounds are known. See U.S. Pat. No. 3,454,701. The patent states that clonidine may be formulated for oral, parenteral (i.e. hypodermic injection), or rectal administration to treat hypertension.
U.S. Pat. No. 3,202,660 indicates clonidine is useful for vasoconstrictor therapy. For use in such therapy it is mixed with inert carriers to adapt it for topical application to mucuous membranes such as the nasal cavity.
U.S. Pat. No. 3,190,802 says that clonidine is also useful as a pilomotor agent in shaving compositions. As such it is applied to facial skin in the form of a shaving lotion, soap, or cream.
Clonidine is also useful for treating migraine as described in U.S. Pat. No. 3,666,861 and for treating glaucoma as described in the literature references E. Edelhauser, V. Nemetz, Klin, Mbl. Augenheilkunde 160 (1972) 188 and R. Jahnke, H.W. Thumm, Klin. Mbl. Augenheilk. 161 (1972) 73.
Many factors bear on the practicability of administering a particular drug transdermally to provide therapy for a given condition. Among other requirements, the drug must not damage the skin over prolonged contact therewith (e.g. affect the skin structure adversely, or cause irritation, allergy, or sensitization). It must not be unduly immobilized by the skin. And, it must be capable of permeating through a relatively small area of skin at a therapeutically effective rate. Clonidine unexpectedly meets these requirements.